CN113456784B

CN113456784B - Traditional Chinese medicine composition for treating chronic recurrent eczema

Info

Publication number: CN113456784B
Application number: CN202110958138.2A
Authority: CN
Inventors: 陈达灿; 莫秀梅; 刘俊峰; 叶思祺; 贾金靖; 晏烽根; 李红毅
Original assignee: Guangdong Hospital of Traditional Chinese Medicine
Current assignee: Guangdong Hospital of Traditional Chinese Medicine
Priority date: 2021-08-20
Filing date: 2021-08-20
Publication date: 2022-06-10
Anticipated expiration: 2041-08-20
Also published as: CN113456784A

Abstract

The invention relates to a traditional Chinese medicine composition for treating chronic recurrent eczema, which consists of effective components and medically acceptable auxiliary materials, and is characterized in that the effective components are prepared from the following raw material medicines in percentage by weight: 15-19% of honeysuckle, 9-11% of sophora flower, 8-10% of curcuma zedoary, 8-10% of rhizoma atractylodis, 10-12% of bighead atractylodes rhizome, 20-25% of coix seed, 10-12% of radix rehmanniae and 9-11% of divaricate saposhnikovia root. The traditional Chinese medicine composition has the effects of detoxifying, strengthening body resistance, eliminating dampness and activating blood circulation, and can obviously improve the rash of patients with chronic recurrent eczema and relieve pruritus.

Description

Traditional Chinese medicine composition for treating chronic recurrent eczema

Technical Field

The invention relates to medical preparations, in particular to a medicinal preparation with an undefined structure of traditional herbal medicines, which is suitable for treating chronic recurrent eczema.

Background

Eczema (Eczema) is an inflammatory disease of skin with exudation tendency caused by various internal and external factors, is accompanied by obvious pruritus, is recurrent and easy to become chronic, seriously influences the life quality of patients, and is one of common skin difficult diseases. Global epidemiological studies have shown that the general trend of eczema prevalence is increasing, especially in developed countries and in rapidly urbanized, westernized areas. The prevalence rate of general population in China is about 7.5%, and is close to that of western countries. Prevention and treatment of eczema is a hotspot and a difficulty which are concerned in the fields of skin and allergic diseases all over the world at present.

The cause and mechanism of eczema is not completely clear, and it is thought that internal factors such as immune dysfunction and skin barrier dysfunction interact with external factors such as environmental factors and microorganisms. Most of the western medicines have treatment methods for eczema, but the eczema is easy to recur, and no effective treatment method for completely curing the eczema exists so far. Current standard therapies for eczema include topical corticosteroids, anti-inflammatory calcineurin inhibitors, systemic antihistamines to adjunctively treat pruritus, avoiding triggering or exacerbating factors. In severe, refractory cases, systemic glucocorticoid therapy or treatment with immunosuppressive agents such as cyclophosphamide and the like may be considered. Western medicines for treating eczema have side effects which are not negligible, for example, antihistamine medicines can cause serious side effects of lethargy, dry mouth, lassitude, even arrhythmia and the like of patients; long-term and wide-range external application of hormone medicines, especially potent preparations, can cause local adverse reactions such as skin thinning, pigmentation, hypopigmentation, telangiectasia and the like, and systemic malabsorption such as hypothalamus-pituitary-epinephrine axis and the like; calcineurin inhibitors (such as tacrolimus ointment) have no hormone side effects, have adverse reactions mainly including burning and irritation, and have potential risks of skin cancer; immunosuppressive agents used in critically ill patients are common side effects of these agents, such as hepatotoxicity and renal toxicity. The current therapeutic goals of eczema are to control symptoms, reduce recurrence, and improve the quality of life of patients.

The clinical verification of the traditional Chinese medicine for treating eczema for thousands of years proves that the traditional Chinese medicine has an outstanding curative effect. Eczema belongs to the categories of eczema, impetigo, eczema papulosa and the like in the traditional Chinese medicine. The Ming Dynasty Chen Shi Gong is recorded in "Zheng Zhu Zheng Zhong Zheng Pi and Yan Zhu Zheng Zhong (orthodox treatment of surgery)", which concentrates the theoretical essence of treatment of eczema. However, the etiology and pathogenesis of eczema are the important factors of toxic and stasis besides the internal injury of spleen and stomach and the invasion of damp-heat. Spleen failing to transport and transform, food essence failing to distribute, nutrient-defensive disharmony, dampness generating internally, dampness being sticky and greasy and easily mixing with heat, damp-heat accumulating for a long time to generate wind and transform toxin, obstructing meridians and collaterals and stagnating qi and blood, marked by excess of damp-heat stasis toxin and deficient essence of spleen and stomach. Clinical tests prove that the traditional Chinese medicine composition can effectively improve clinical symptoms, relieve pruritus, and is safe and reliable.

The patent application with publication number CN101322814A discloses a traditional Chinese medicine for treating eczema, which is prepared from 11 kinds of Chinese medicinal herbs including honeysuckle flower, flavescent sophora root, dried rehmannia root, white peony root, poria cocos, atractylodes rhizome, coix seed, dittany bark, broom cypress fruit, tree peony bark and plantain seed. The compatibility principle of the traditional Chinese medicines is that honeysuckle, radix sophorae flavescentis and radix rehmanniae are used as monarch medicines together for clearing heat, removing toxicity and removing dampness; cortex dictamni, fructus kochiae and cortex moutan radicis are used for cooling blood, dispelling wind and arresting itching and are used as ministerial drugs; radix Paeoniae alba, Poria, rhizoma Atractylodis, and Coicis semen are used as adjuvant drugs for invigorating qi, invigorating spleen, and eliminating dampness; semen plantaginis is a guiding drug, and has the effects of clearing heat, promoting urination, excreting dampness, treating stranguria, and inducing dampness to descend and discharge out of the body. The compatibility of the medicines can achieve the effects of clearing away heat and toxic material, removing dampness, cooling blood, dispelling wind and arresting itching. However, the prescription has a lot of medicinal herbs, and the other herbs except for atractylodes rhizome (warm in nature) and tuckahoe (neutral in nature) are cold and cool herbs, so the whole medicinal property is cold and cool, and the prescription is not suitable for long-term use for patients with long-term disease course and healthy qi deficiency. In addition, the monarch drugs of the traditional Chinese medicines consist of three raw material medicines of honeysuckle, radix sophorae flavescentis and radix rehmanniae recen, so that the potency of the drugs is dispersed, and the curative effect is influenced (li ji, lian jianwei master edition, the chapter of prescriptions, the press of traditional Chinese medicine, 4 th edition of 8 months in 2016, page 17). With the continuous increase of eczema patients and the characteristic that the eczema condition is easy to relapse, the finding of a medicine which has less medicine flavor, mild medicine property, easy long-term use and obvious effect of treating chronic recurrent eczema has important practical significance.

Disclosure of Invention

The technical problem to be solved by the invention is to provide the traditional Chinese medicine composition for treating chronic recurrent eczema, which has the effects of detoxifying, strengthening body resistance, removing dampness and activating blood circulation, and has a remarkable effect of treating the chronic recurrent eczema.

The technical scheme for solving the problems comprises the following steps:

the traditional Chinese medicine composition for treating chronic recurrent eczema is composed of effective components and pharmaceutically acceptable auxiliary materials, and is characterized in that the effective components are prepared from the following raw material medicines in percentage by weight:

15-19% of honeysuckle, 9-11% of sophora flower, 8-10% of curcuma zedoary, 8-10% of rhizoma atractylodis, 10-12% of bighead atractylodes rhizome, 20-25% of coix seed, 10-12% of radix rehmanniae (radix rehmanniae recen) and 9-11% of divaricate saposhnikovia root.

In the scheme, the optimal weight percentage of the raw material medicines is 17% of honeysuckle, 10% of sophora flower, 9% of curcuma zedoary, 9% of rhizoma atractylodis, 11% of bighead atractylodes rhizome, 23% of coix seed, 11% of radix rehmanniae and 10% of divaricate saposhnikovia root.

The traditional Chinese medicine composition is prepared from the following effective components by the following method:

(1) decocting the raw materials in water for three times according to a proportion, wherein after the raw materials are added with 10 times of water for soaking for 1 hour for the first time, the raw materials are decocted for 1.5 hours, and 6 times of water is respectively added for the second time and the third time, and the raw materials are decocted for 1 hour; mixing the three decoctions, and filtering to obtain filtrate;

(2) concentrating the filtrate obtained in step (1) at 60 deg.C under reduced pressure to relative density of 1.05-1.20, spray drying, and pulverizing into fine powder to obtain the effective component.

The traditional Chinese medicine composition can be prepared into oral preparations such as granules, capsules or tablets, and the oral preparations are prepared from the effective components and medically acceptable auxiliary materials according to a conventional method.

The formula of the traditional Chinese medicine composition is composed of eight Chinese medicines of honeysuckle, sophora flower, curcuma zedoary, rhizoma atractylodis, bighead atractylodes rhizome, coix seed, radix rehmanniae and divaricate saposhnikovia root, and honeysuckle flower in the formula is sweet and cold in nature and tastes sweet and cool, and is a monarch medicine for clearing heat and removing toxicity; flos sophorae cools blood and clears damp heat, rhizoma zedoariae activates blood and breaks stasis, makes damp heat transformed and qi and blood flowing through, and the two medicines assist the monarch medicine in detoxifying and are used as ministerial medicines together; the rhizoma atractylodis is used for eliminating dampness and enlivening spleen, the rhizoma atractylodis macrocephalae is used for tonifying spleen and qi, the semen coicis is used for tonifying spleen and excreting dampness, the combination is used for regulating middle energizer, the radix rehmanniae is used for clearing heat and cooling blood, nourishing yin and promoting fluid production, and the rhizoma atractylodis is used for preventing yin from being damaged due to dampness, and the four medicines are used as adjuvant medicines; fang Feng is a guiding drug for spleen meridian and also has the action of relieving itching. The medicines are compatible and have the effects of detoxifying, strengthening body resistance, eliminating dampness and activating blood circulation. The whole formula tightly buckles the pathogenesis, detoxifies and strengthens the body resistance, can coordinate spleen and stomach, dispel damp-heat, regulate qi and blood, detoxicate and remove blood stasis, and thus has quick effect.

The beneficial effects of the traditional Chinese medicine composition are further proved by the following researches.

First, clinical research

1. The source of the cases: patients with chronic recurrent eczema are treated by the dermatology clinic of the second subsidiary hospital of Guangzhou Chinese medicine university (traditional Chinese medicine hospital in Guangdong province) in 6-2021 month in 2020.

1.1 diagnostic criteria

Western diagnostic criteria: refer to Zhao Zhang "Chinese clinical dermatology" (2009 edition) for the diagnosis of eczema. Eczema is diagnosed according to the medical history, the form and the course of the rash of the patient: generally, eczema and eruption are polymorphic, mainly erythema, pimple and herpes dunghill, the central part of the rash is obvious, the rash gradually disperses to the periphery, the boundaries are unclear, the rash is diffuse and tends to exude, and the pruritus is severe. Chronic eczema is characterized by the pachynsis, infiltration, reddish brown or grayish skin, pigmentation, rough surface, or scabbing due to scratching, and various lichen changes, which occur frequently and repeatedly and have severe pruritus.

1.2 inclusion criteria

Firstly, the age is less than or equal to 6 years and less than or equal to 60 years; secondly, the medicine accords with the diagnosis standard of the western medicine eczema, belongs to chronic recurrent eczema, and voluntarily participates in the research and signs an informed consent (patients under 18 years old need to sign by guardians at the same time).

1.3 exclusion criteria:

combining diseases such as hypertension, diabetes, cardiovascular and cerebrovascular diseases, Parkinson's disease, infection, malignant tumor and liver/kidney diseases; ② the medicine can be used for curing gastrointestinal tract and liver and gall inflammatory diseases, gastrointestinal tract diseases, tuberculosis, parasite, etc.; ③ special people: pregnant/lactating women, psychiatric patients, and the like; fourthly, other skin diseases needing to be treated are combined, such as psoriasis, alopecia areata, scabies and the like; patients who have been treated with immunosuppressive agents, glucocorticoids or antibiotics within 12 weeks.

2. Method of treatment

The granules of the following example 1 are taken with warm water 1 bag each time and 2 times a day, and the treatment course is 8 weeks.

3. Evaluation of clinical efficacy

3.1 Main therapeutic index

The Eczema Area and Severity Index (EASI) are used as main efficacy evaluation indexes. The method carries out comprehensive integration according to the skin damage symptoms and severity degrees of different parts and the size of the occupied area. The highest score was 72.

3.2 Secondary efficacy index

The eczema self-scoring scale (POEM), which is filled out by patients/parents of eczema in approximately 1 week. The maximum score was 28.

② degree of pruritus: the patient or his father were convinced of the ability to answer the questions properly, giving him/her the indication of the corresponding point on the 10cm evaluation scale where the average of the last 3 diurnal pruritus levels was (see fig. 1).

Third, the investigator overall evaluation (IGA), which was performed by the physician on the patient's rash for a maximum score of 5.

The above indexes were evaluated 1 time each before (0 week), 2 weeks, 4 weeks, 6 weeks, and 8 weeks of treatment.

Safety evaluation

Adverse events were documented for the patients throughout the study.

4. Data management and statistical analysis method

And (3) establishing a database by adopting an EPIdata3.1 software package, inputting a test result, performing data proofreading by using a software module, converting without errors to generate an SPSS18.0 statistical analysis software package database, and performing database maintenance such as data cleaning, distribution inspection and the like.

Calculating the mean plus or minus standard deviation of the measured data according to normal distribution; calculating median (four-quadrant spacing), minimum and maximum values of the skewness distribution; the count data is used to calculate the composition ratio and the rate. Measurement data: paired t Test (or paired Signed rank sum Test) was used for the group's own pre-and post-comparisons. Multiple observation point analyses were corrected using repeated measures analysis of variance (less than spherical test, using G-G (Greenhouse-Geisser); test level α is 0.05.

5. Results of the study

5.1 Baseline characteristics

A total of 47 patients were included in the study, and the baseline profile of the patients is detailed in table 1.2 of the patients were missed at 2 weeks, and 45 patients who had first-time efficacy evaluation after the administration entered the intention analysis (ITT). During the treatment process of 45 patients, 3 patients have satisfactory subjective curative effect, and the treatment is ended in advance; 1 patient takes the medicine for 4 weeks and stops taking the medicine due to pregnancy; 1 case was stopped due to upper respiratory tract infection, 1 case was relapsed due to urticaria, and the remaining 6 patients were missed.

Table 1 baseline characteristics of subjects prior to treatment (n,

Median(P₂₅-P₇₅))

5.2 clinical efficacy

5.2.1 Eczema Area and Severity Index (EASI)

After treatment, repeated measurement analysis of variance is adopted for EASI scoring at each observation point, and the result indicates that the spherical test difference has statistical significance (P <0.001), so a G-G (Greenhouse-Geisser) model is selected for correction, analysis indicates that the repeated observation comparison difference has statistical significance (F is 7.473 and P is <0.001), the repeated measurement EASI index is in a descending trend along with the treatment time, and the difference has statistical significance (F is 81.010 and P is <0.001), which is shown in figure 2.

The EASI before and after treatment has statistical significance (P <0.10) through the normal test, each observation time point after treatment is compared with that before treatment, and the results are shown by adopting the paired sign rank sum test, except that the comparison difference between 2 weeks after treatment and before treatment has no statistical significance (P >0.05), the comparison differences between 4 weeks, 6 weeks and 8 weeks after treatment have statistical significance (P <0.05) compared with that before treatment, and the table 2 shows.

TABLE 2 paired symbol rank sum test for each observation time point of the patient's EASI before and after treatment

Note: p < 0.05.

5.2.2 eczema patient self-score (POEM)

After treatment, POEM scores at each observation point are analyzed by repeated measurement variance, and the result indicates that the difference of spherical test has statistical significance (P is 0.002), so a G-G (Greenhouse-Geisser) model is selected for correction, analysis indicates that the difference of multiple observations and comparison has statistical significance (F is 4.109 and P is 0.008), the POEM scores of multiple measurements show a descending trend along with the change of time, and the difference has statistical significance (F is 151.226 and P is less than 0.001), which is shown in figure 3.

The difference between POEM before and after treatment has statistical significance (P <0.10) through the normality test, each observation time point after treatment is compared with POEM before treatment, and the results of the pairing symbol rank sum test show that the difference has statistical significance (P <0.05) when POEM 2 weeks, 4 weeks, 6 weeks and 8 weeks after treatment is compared with POEM before treatment, and the difference is shown in the table 3.

TABLE 3 paired symbol rank sum test for pre-and post-treatment POEM observation points

Note: p < 0.05.

5.2.3 Pruritus index

After treatment, repeated measurement analysis of variance is adopted for the pruritus indexes at each observation time point, and the result indicates that the difference of the spherical test has statistical significance (P is 0.001), so a G-G (Greenhouse-Geisser) model is selected for correction, the analysis indicates that the comparison difference of multiple observations has statistical significance (F is 4.395, P is 0.006), the comparison difference of multiple measured pruritus indexes after treatment for 4 weeks, 6 weeks and 8 weeks has no statistical significance (P is 0.05) except that the comparison difference of the pruritus indexes after treatment for 2 weeks and before treatment has no statistical significance, and the differences have statistical significance (F is 274.992, P is 0.001) after treatment and before treatment, which is shown in figure 4.

The evaluation of the itch index before and after treatment is carried out by a normal test, the difference has statistical significance (P <0.10), each observation time point after the treatment is compared with the observation time point before the treatment, and the results are shown by adopting a paired sign rank sum test, and the difference has statistical significance (P <0.05) when compared with the observation time point before the treatment after 4 weeks, 6 weeks and 8 weeks after the treatment except that the difference between 2 weeks after the treatment and the comparison before the treatment has no statistical significance (P >0.05), and the difference is shown in a table 4.

TABLE 4 paired symbol rank sum test for patient before and after treatment itch index scores at each observation time point

Note: p < 0.05.

5.2.4 investigator general evaluation (IGA)

Repeated measurement analysis of variance is adopted for each observation time point index IGA score after treatment, the result indicates that the test meets the spherical test (P & gt 0.05), the analysis indicates that the comparison difference of multiple observations has statistical significance, the IGA score of multiple measurements shows a descending trend along with the time change, and the difference has statistical significance (F & gt 523.566, P & lt 0.001), and the figure 5 shows that the test is simple, convenient and fast to use.

The difference between the IGA score before and after treatment is statistically significant (P <0.10) by the normality test, and the difference between each observation time point after treatment and before treatment is statistically significant (P <0.05) by the pairing symbol rank sum test, as can be seen from the results of comparison between 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment and before treatment, as shown in table 5.

TABLE 5 paired symbol rank-sum test for pre-treatment and post-treatment IGA scores for each observation time point

Note: p < 0.05.

5.2.4 adverse events

In the research process, 1 patient has upper respiratory tract infection, and 1 patient has urticaria and relapse, which are not directly related to the tested medicine; no serious adverse events occurred in the study. No adverse reaction related to the traditional Chinese medicine is found in the research.

6. Conclusion

The traditional Chinese medicine composition can obviously improve the severity of skin damage of patients with chronic recurrent eczema, relieve pruritus and improve subjective symptoms of the patients. In the clinical observation process, no adverse reaction of the medicine is found, which indicates that the medicine is safe and effective.

Second, animal experiment

Materials and instruments:

DNCB (2, 4-dinitrochlorobenzene, 2, 4-dinitrochlorobenzene), commercially available from Sigma;

dexamethasone, available from Sigma;

mouse Th1/Th2/Th17 photoprying Kit available from BD Pharmingen

Mouse Regulatory T Cell stabilizing Kit available from Thermo Fisher corporation

APC/Cyanine7 anti-mouse CD3 epsilon Antibody, available from BioLegend

APC/Cyanine7 anti-mouse CD8a Antibody available from BioLegend

Mouse spleen lymphocyte separation kit purchased from Tianjin City restricted ocean biology Ltd

Mouse spleen cells were obtained from the tertiary ocean organism, Inc. of Tianjin, using low adsorption siliconized tubes

Leukocyte Activation Cocktail,with BD GolgiPlug^TMFrom BD Pharmingen

X-Vivo 15 serum-free cell culture Medium, available from Lonza

Novocyte D2060R flow cytometer available from Agilent

Mouse IgE ELISA kit available from Abcam corporation

Mouse IFN-gamma Quantikine ELISA Kit available from R & D Systems

Mouse IL-4 Quantikine ELISA Kit available from R & D Systems

Mouse IL-17 Quantikine ELISA Kit available from R & D Systems

Mouse TGF beta 1 ELISA kit, purchased from Abcam corporation

Mouse IL-10 Quantikine ELISA Kit available from R & D Systems

Experimental animals: 24 male Balb/C mice with the weight of 18-22g are purchased from the Guangdong province medical animal experiment center;

2 method of experiment

2.1 establishment of atopic eczema mouse model:

male Balb/C mice were shaved on their backs, sensitized with 200. mu.L of 1% (prepared as a solvent from a base solution prepared by mixing acetone and olive oil at a ratio of 3: 1) (150. mu.l for external application to the back and 20. mu.l for external application to both ears), and then alternately stimulated 3 times per week with 0.2% DNCB. Meanwhile, scoring, photographing and ear thickness measurement are carried out every week, and materials are taken 28 days after the experiment.

2.2 dosing regimen:

(1) mice were randomly divided into 6 mice per group as follows:

A. normal control group (Normal control group)

B. Atopic eczema model group (model group)

C. Model group + Experimental drugs (Experimental group)

D. Model group + dexamethasone positive control drug (positive control group)

(2) The normal group and the model group were gavaged with physiological saline daily, the test group was gavaged with granules of example 1 given below after being dissolved in water daily, the administration dose was 14.41g/kg by weight of the drug substance (dose (g/kg) ═ standard weight adult dose × coefficient ═ 95g/60kg) × 9.1 ═ 14.41g/kg), and the dexamethasone positive control group was gavaged with dexamethasone (Sigma, D4902-25MG) 1MG/kg daily. The experimental procedure is shown in FIG. 6.

2.3 mice skin lesion severity score:

SCORAD score in mice: erythema/hemorrhage, crust/dryness, exfoliation/erosion, edema 4 indices, each severity still being on a scale of 0-3, 0 being none, 1 being light, 2 being medium, 3 being heavy. The total score is the score of SCORAD. Pictures were taken and the SCORAD score of mice was calculated.

2.4 mouse spleen cell Th1/Th2/Th17/Treg ratio determination:

(ii) after the mice are sacrificed, the spleens of the mice are removed and placed in 6-well plates containing HBSS (Hank's Balanced Salt Solution);

secondly, grinding the spleen of the mouse by using the head of the injector, and sieving the spleen by using a 70-micron cell sieve;

thirdly, counting the cells after sieving, calculating the total number of the cells, then diluting the cells by using a sample diluent in the separation kit, and adjusting the concentration value of the cells to be 1 multiplied by 108/ml;

fourthly, the resuspended cells are paved on the separation liquid, a silicified tube is used, the volume ratio of the two is 1:1(4 ml: 4ml),

placing the well paved cells in a centrifuge for 500g and 30 min;

sixthly, sucking the middle layer cells of the separation liquid after the centrifugation is finished;

seventhly, adding 10ml of HBSS to wash the cells twice, and counting the cells;

(v) diluting with X-VIVO medium to adjust cell concentration to 1 × 108 cells/ml

Ninthly, absorbing 100 mu l of cell suspension and stimulating the culture solution; culturing for 8 hours under the culture condition of a 24-pore plate and a culture volume of 1ml by adding a stimulant; subsequent staining analysis of Th1/Th2/Th 17;

another 100. mu.l of cell suspension was aspirated for Treg staining.

2.5 mouse serum differential cytokine assay:

the routine procedure was performed according to ELISA kits.

2.6 statistical methods:

statistical methods statistical analysis was performed using SPSS 19.0 software, with data expressed as mean ± standard error. The comparison between the two groups adopts t test; the comparison between three and more groups was performed by analysis of variance, and the comparison between two groups was examined by LSD. P <0.05 indicates that the difference is statistically significant.

3, results:

3.1 Experimental drugs can reduce skin lesion expression in atopic eczema mouse model

The skin damage and pathological characteristics of the mouse model induced by DNCB sensitization are very close to the expression of human atopic eczema, and compared with a model group, the mouse model induced by DNCB sensitization has the advantages that the symptoms of erythema and scale are reduced and the skin damage is thinned after the stomach is perfused with experimental drugs (figure 7 and figure 8); the dermatitis scores of the experimental groups are obviously reduced (p is less than 0.01) (table 6), the ear swelling degrees are obviously reduced (p is less than 0.001) (figure 9), and the dermatitis scores and the ear swelling degrees of the positive control groups are both obviously reduced (p is less than 0.001 and p is less than 0.001) (table 6 and figure 9).

TABLE 6 mouse dermatitis score

^###P<0.001vs. normal control group;^**P<0.01,^***P<0.001vs. model set

3.2 the experimental medicine can improve the proportion of Th1 cells of atopic eczema mice and reduce the proportion of Th2, Th17 and Treg cells

Separating Native CD4+ T cells of the mouse spleen, and reducing the ratio of Th1 cells of the mouse spleen in an atopic eczema model group (P is less than 0.001) and obviously increasing the ratio of Th2 cells, Th17 cells and Treg cells (P is less than 0.001) compared with the normal group by using the ratio of Th1, Th2 cells, Th17 cells and Treg cells of a flow cytometer; after 4 weeks of the gavage treatment of the experimental drug, the proportion of Th1 cells (P is less than 0.01) of the mice can be improved, and the proportion of Th2, Th17 and Treg cells (P is less than 0.001) can be reduced; after the positive control group was administered with gastric lavage, the proportions of Th1, Th2, Th17 and Treg cells were all significantly reduced (P <0.001) (FIG. 10).

3.3 the experimental drugs can reduce the expression of IgE and IL-17 in the serum of atopic eczema mice

ELISA detects the content of each cytokine in mouse serum, so that the IgE and IL-17 of the model group mouse are obviously increased (P is less than 0.001) and the IFN-gamma is obviously reduced (P is less than 0.05) compared with the normal control group mouse; after the treatment of the experimental drug, the IgE and IL-17 in the serum of the mouse can be obviously reduced (P is less than 0.001, P is less than 0.05), and the total IgE and IL-17 in the serum of the mouse can be obviously reduced by a positive control group (P is less than 0.001, P is less than 0.01) (figure 11).

4 conclusion

The research uses a classical atopic eczema animal model to research the specific pharmacodynamic mechanism of an experimental drug, and the result shows that the experimental drug can obviously improve the skin lesion severity of a mouse, reduce the dermatitis score and improve the ear swelling degree, thereby proving the clinical curative effect. Meanwhile, experimental medicines are found to restore the balance disorder of mouse Th1/Th2/Th17/Treg and reduce the expression of IgE and IL-17.

Immune balance disorder is one of the important links of the main pathogenesis of atopic eczema, which is thought to be an immune reaction mainly based on Th2, and release a series of cytokines to cause the adjustment imbalance of Th1/Th2 and further aggravate barrier dysfunction to form a malignant cycle, and recent researches show that the abnormality of the number and the function of Th17 and Treg cells plays an important role in the pathogenesis, and prove that Th17 and Treg are involved in the pathogenesis of atopic eczema. The research shows that the experimental drug can regulate the imbalance of Th1/Th2, also can regulate abnormal Th17 and Treg cell proportion, and reduce the expression of IL-17, thereby demonstrating that the experimental drug plays a role in regulating the integral immune imbalance of atopic eczema Th1/Th2/Th 17/Treg.

Drawings

Fig. 1 is a schematic structural view of a scale for evaluating the average level (or degree) of itching.

Figure 2 is a line graph of variation in EASI score at each observation time point after treatment of the patient.

Fig. 3 is a line graph showing the change in POEM score at each observation point after treatment of the patient.

Fig. 4 is a line graph of the change in itch index at each observation point after treatment of the patient.

Figure 5 is a line graph showing the change in IGA score at each observation time point after treatment of the patient.

Figure 6 is a schematic diagram of a molding and dosing regimen.

FIG. 7 is a photograph showing the skin expression of a mouse, wherein (A) is a normal control group; (B) the figure is a model group; (C) the figure is an experimental group; (D) the figure is a positive control group.

Fig. 8 is a photomicrograph (scale bar 100 μm) of HE staining pathology of mouse skin tissue, in which panel (a) is a normal control group; (B) the figure is a model group; (C) the figure is an experimental group; (D) the figure is a positive control group.

FIG. 9 is a histogram of the degree of swelling in mouse ears (### P <0.001 vs. normal control group;. P <0.001 vs. model group).

FIG. 10 is a histogram of the ratio of Th1/Th2/Th17/Treg cells in each group of mice, wherein the graph (A) is a histogram of the ratio of Th1 cells in each group of mice; (B) the figure is a histogram analysis chart of Th2 cell proportion of each group of mice; (C) the figure is a histogram analysis chart of Th17 cell proportion of each group of mice; (D) the figure is a histogram analysis of the proportion of Treg cells in each group of mice (# P <0.001 vs. normal control; P < 0.01; P <0.001 vs. model group).

FIG. 11 is a graph showing a statistical analysis of the levels of various cytokines in mouse serum, wherein (A) is a graph showing a statistical analysis of serum IgE; (B) the figure is a statistical analysis chart of serum IFN-gamma; (C) the figure is a serum IL-4 statistical analysis chart; (D) the figure is a serum IL-17 statistical analysis chart; (E) the figure is a serum TGF-beta statistical analysis chart; (F) the figure is a serum IL-10 statistical analysis figure (# P <0.05, # P <0.001 vs. normal control group, # P <0.05, # P < 0.01, # P <0.001 vs. model group).

The specific implementation mode is as follows:

example 1 (granules)

[ CHEM ] flos Lonicerae 742g, flos Sophorae 437g, Curcumae rhizoma 393g, rhizoma Atractylodis 393g, Atractylodis rhizoma 480g, Coicis semen 1004g, radix rehmanniae 480g, and radix Saposhnikoviae 437 g.

[ PREPARATION METHOD ] A

(1) Decocting the above 8 materials with water for three times, soaking in 10 times of water for 1 hr for the first time, decocting for 1.5 hr, adding 6 times of water for the second and third times, decocting for 1 hr, mixing decoctions, and filtering to obtain filtrate;

(2) concentrating the filtrate at 60 deg.C to relative density of 1.05-1.20, spray drying, and pulverizing into fine powder;

(3) adding appropriate amount of steviosin, (dextrin, sucrose powder 7:1), mixing, granulating, drying, making into 1000g, and packaging into 10 g/bag.

Example 2 (granules)

[ CHEM ] flos Lonicerae 663g, flos Sophorae 436g, rhizoma Curcumae 392g, rhizoma Atractylodis 522g, Coicis semen 1045g, radix rehmanniae 479g, and radix Saposhnikoviae 436 g.

[ PREPARATION METHOD ] A

(1) Same as example 1;

(2) same as example 1;

(3) adding appropriate amount of steviosin, dextrin and sucrose powder, mixing, granulating, drying, making into 1000g, and packaging into 10 g/bag.

Example 3 (granules)

[ CHEM ] flos Lonicerae 809g, flos Sophorae 476g, Curcumae rhizoma 389g, rhizoma Atractylodis 389g, Atractylodis rhizoma 442g, Coicis semen 909g, radix rehmanniae 475g, and radix Saposhnikoviae 476 g.

[ PREPARATION METHOD ]

(1) Same as example 1;

(2) same as example 1;

(3) adding appropriate amount of steviosin and dextrin, mixing, granulating, drying, making into 1000g, and packaging into 10 g/bag.

Example 4 (Capsule)

[ CHEM ] flos Lonicerae 708g, flos Sophorae 442g, Curcumae rhizoma 398g, rhizoma Atractylodis 432g, Atractylodis rhizoma 528g, Coicis semen 972g, radix rehmanniae 486g, radix Saposhnikoviae 399 g.

[ PREPARATION METHOD ]

(1) Same as example 1;

(2) same as example 1;

(3) adding appropriate amount of starch, mixing, granulating, and making into capsule 2000.

Example 5 (tablet)

[ prescription ] 776g flos Lonicerae, 431g flos Sophorae Immaturus, 388g rhizoma Curcumae, 353g rhizoma Atractylodis, 474g rhizoma Atractylodis Macrocephalae, 950g semen Coicis, 518g radix rehmanniae, 475g radix Saposhnikoviae.

[ PREPARATION METHOD ]

(1) Same as example 1;

(2) same as in example 1;

(3) adding appropriate amount of starch, mixing, granulating, and making into tablet 2000.

Claims

1. The traditional Chinese medicine composition for treating chronic recurrent eczema is composed of effective components and medically acceptable auxiliary materials, and is characterized in that the effective components are prepared from the following raw material medicines in percentage by weight:

15-19% of honeysuckle, 9-11% of sophora flower, 8-10% of curcuma zedoary, 8-10% of rhizoma atractylodis, 10-12% of bighead atractylodes rhizome, 20-25% of coix seed, 10-12% of radix rehmanniae and 9-11% of divaricate saposhnikovia root.

2. The traditional Chinese medicine composition for treating chronic recurrent eczema as claimed in claim 1, wherein the effective components are prepared from the following raw material medicines in percentage by weight:

17% of honeysuckle, 10% of sophora flower, 9% of curcuma zedoary, 9% of rhizoma atractylodis, 11% of bighead atractylodes rhizome, 23% of coix seed, 11% of radix rehmanniae and 10% of divaricate saposhnikovia root.

3. The traditional Chinese medicine composition for treating chronic recurrent eczema as claimed in claim 1 or 2, wherein the effective components are prepared by the following method:

(1) the raw materials are taken according to the proportion and are added with water for decoction for three times, wherein after the raw materials are added with 10 times of water for soaking for 1 hour for the first time, the raw materials are decocted for 1.5 hours, and 6 times of water is added for the second time and the third time respectively for decoction for 1 hour; mixing the three decoctions, and filtering to obtain filtrate;

4. The traditional Chinese medicine composition for treating chronic recurrent eczema as claimed in claim 3, wherein the traditional Chinese medicine composition is granules, capsules or tablets.